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UPLC-MS/MS method for the simultaneous quantification of sofosbuvir, sofosbuvir metabolite (GS-331007) and daclatasvir in plasma of HIV/HCV co-infected patients.
J Chromatogr B Analyt Technol Biomed Life Sci. 2018 Jan 15; 1073:183-190.JC

Abstract

Direct-acting antiviral agents (DAAs) represent the major advance in hepatitis C virus (HCV) infection treatment leading to extremely high eradication rates in HCV mono- and HIV/HCV co-infected patients. In this scenery, availability of Therapeutic Drug Monitoring (TDM) is of interest to assess plasma concentrations to prevent either therapeutic failure due to suboptimal medication adherence and drug-drug interactions or avoid adverse events. Aim of this study was to develop and validate an Ultra-Performance Liquid Chromatography Mass Spectrometry (UPLC-MS/MS) method for the simultaneous quantification of sofosbuvir, sofosbuvir metabolite (GS-331007), and daclatasvir in human plasma. A simple protein precipitation was applied by adding 200 μL acetonitrile with internal standard 6,7-Dimethyl- 2,3-di(2-pyridyl) quinoxaline to 100 μL plasma sample. Drug separation was performed on analytical C-18 Luna Omega column (50 mm × 2.1 mm I.D.) with particle size of 1.6 μm. The mobile phase consisting of water containing 0.1% formic acid and acetonitrile at flow 0.4 mL/min and a gradient run time of 3.5 min. The injection volume was 10 μL. Anti-HCV drugs were detected in positive electrospray ionization mode. The full scan mass spectral analyses of sofosbuvir, GS-331007, daclatasvir and quinaxoline showed protonated molecule ions and transitions m/z: 530.098 → 243.02, 260.93 → 112.94, 739.4 → 339.27 and 313.03 → 77.99 respectively. The linearity of standard curves was excellent (r2 > 0.99), the absolute recovery of anti-HCV drugs ranged between 95 and 98%, and both imprecision and inaccuracy were <15% according to FDA guidelines. The UPLC-MS/MS method was applied to 16 plasma samples of as many HIV/HCV co-infected patients treated with sofosbuvir and daclatasvir. While sofosbuvir was not detectable in all samples, the median plasma concentrations of daclatasvir and GS-331007 were 223.6 ± 319.56 ng/mL and 537.11 ± 242.09 ng/mL, respectively. In conclusion, we describe an UPLC-MS/MS method allowing the simultaneous quantification of sofosbuvir, GS-331007 and daclatasvir in plasma samples. The method was sensitive, specific, robust, and time-saving.

Authors+Show Affiliations

Laboratory of Cellular Immunology and Pharmacology, National Institute for Infectious Diseases "Lazzaro Spallanzani", IRCCS, Rome, Italy.Laboratory of Cellular Immunology and Pharmacology, National Institute for Infectious Diseases "Lazzaro Spallanzani", IRCCS, Rome, Italy.Clinical Department, National Institute for Infectious Diseases "Lazzaro Spallanzani", IRCCS, Rome, Italy.Clinical Department, National Institute for Infectious Diseases "Lazzaro Spallanzani", IRCCS, Rome, Italy.Clinical Department, National Institute for Infectious Diseases "Lazzaro Spallanzani", IRCCS, Rome, Italy.Clinical Department, National Institute for Infectious Diseases "Lazzaro Spallanzani", IRCCS, Rome, Italy.Laboratory of Cellular Immunology and Pharmacology, National Institute for Infectious Diseases "Lazzaro Spallanzani", IRCCS, Rome, Italy. Electronic address: chiara.agrati@inmi.it.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29276983

Citation

Notari, Stefania, et al. "UPLC-MS/MS Method for the Simultaneous Quantification of Sofosbuvir, Sofosbuvir Metabolite (GS-331007) and Daclatasvir in Plasma of HIV/HCV Co-infected Patients." Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences, vol. 1073, 2018, pp. 183-190.
Notari S, Tempestilli M, Fabbri G, et al. UPLC-MS/MS method for the simultaneous quantification of sofosbuvir, sofosbuvir metabolite (GS-331007) and daclatasvir in plasma of HIV/HCV co-infected patients. J Chromatogr B Analyt Technol Biomed Life Sci. 2018;1073:183-190.
Notari, S., Tempestilli, M., Fabbri, G., Libertone, R., Antinori, A., Ammassari, A., & Agrati, C. (2018). UPLC-MS/MS method for the simultaneous quantification of sofosbuvir, sofosbuvir metabolite (GS-331007) and daclatasvir in plasma of HIV/HCV co-infected patients. Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences, 1073, 183-190. https://doi.org/10.1016/j.jchromb.2017.12.018
Notari S, et al. UPLC-MS/MS Method for the Simultaneous Quantification of Sofosbuvir, Sofosbuvir Metabolite (GS-331007) and Daclatasvir in Plasma of HIV/HCV Co-infected Patients. J Chromatogr B Analyt Technol Biomed Life Sci. 2018 Jan 15;1073:183-190. PubMed PMID: 29276983.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - UPLC-MS/MS method for the simultaneous quantification of sofosbuvir, sofosbuvir metabolite (GS-331007) and daclatasvir in plasma of HIV/HCV co-infected patients. AU - Notari,Stefania, AU - Tempestilli,Massimo, AU - Fabbri,Gabriele, AU - Libertone,Raffaella, AU - Antinori,Andrea, AU - Ammassari,Adriana, AU - Agrati,Chiara, Y1 - 2017/12/12/ PY - 2017/07/04/received PY - 2017/12/06/revised PY - 2017/12/10/accepted PY - 2017/12/26/pubmed PY - 2018/3/3/medline PY - 2017/12/26/entrez KW - DAA KW - Daclatasvir KW - GS-331007 KW - HCV KW - Liquid chromatograpy- mass spectrometry KW - Sofosbuvir KW - Therapeutic drug monitoring SP - 183 EP - 190 JF - Journal of chromatography. B, Analytical technologies in the biomedical and life sciences JO - J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. VL - 1073 N2 - Direct-acting antiviral agents (DAAs) represent the major advance in hepatitis C virus (HCV) infection treatment leading to extremely high eradication rates in HCV mono- and HIV/HCV co-infected patients. In this scenery, availability of Therapeutic Drug Monitoring (TDM) is of interest to assess plasma concentrations to prevent either therapeutic failure due to suboptimal medication adherence and drug-drug interactions or avoid adverse events. Aim of this study was to develop and validate an Ultra-Performance Liquid Chromatography Mass Spectrometry (UPLC-MS/MS) method for the simultaneous quantification of sofosbuvir, sofosbuvir metabolite (GS-331007), and daclatasvir in human plasma. A simple protein precipitation was applied by adding 200 μL acetonitrile with internal standard 6,7-Dimethyl- 2,3-di(2-pyridyl) quinoxaline to 100 μL plasma sample. Drug separation was performed on analytical C-18 Luna Omega column (50 mm × 2.1 mm I.D.) with particle size of 1.6 μm. The mobile phase consisting of water containing 0.1% formic acid and acetonitrile at flow 0.4 mL/min and a gradient run time of 3.5 min. The injection volume was 10 μL. Anti-HCV drugs were detected in positive electrospray ionization mode. The full scan mass spectral analyses of sofosbuvir, GS-331007, daclatasvir and quinaxoline showed protonated molecule ions and transitions m/z: 530.098 → 243.02, 260.93 → 112.94, 739.4 → 339.27 and 313.03 → 77.99 respectively. The linearity of standard curves was excellent (r2 > 0.99), the absolute recovery of anti-HCV drugs ranged between 95 and 98%, and both imprecision and inaccuracy were <15% according to FDA guidelines. The UPLC-MS/MS method was applied to 16 plasma samples of as many HIV/HCV co-infected patients treated with sofosbuvir and daclatasvir. While sofosbuvir was not detectable in all samples, the median plasma concentrations of daclatasvir and GS-331007 were 223.6 ± 319.56 ng/mL and 537.11 ± 242.09 ng/mL, respectively. In conclusion, we describe an UPLC-MS/MS method allowing the simultaneous quantification of sofosbuvir, GS-331007 and daclatasvir in plasma samples. The method was sensitive, specific, robust, and time-saving. SN - 1873-376X UR - https://www.unboundmedicine.com/medline/citation/29276983/UPLC_MS/MS_method_for_the_simultaneous_quantification_of_sofosbuvir_sofosbuvir_metabolite__GS_331007__and_daclatasvir_in_plasma_of_HIV/HCV_co_infected_patients_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1570-0232(17)31156-X DB - PRIME DP - Unbound Medicine ER -